The present invention relates to a method for the treatment and/or prophylaxis of multiple sclerosis and also the use of erythropoietin for this purpose and also for the production of a drug for intermittent treatment and/or intermittent prophylaxis of multiple sclerosis.
With approx. 80 to 110 cases of multiple sclerosis (MS) per 100,000 persons, multiple sclerosis is the most frequent chronic disease of the central nervous system. A third of patients thereby shows a primary or secondary progressive course of the multiple sclerosis, for which no therapy has been available to date. In particular no therapy is available which would achieve an improvement in the symptoms.
Erythropoietin is a glycoprotein produced naturally in the body, having a molecular weight of 34,000 D. It is an essential growth factor for the production of erythrocytes and was isolated for the first time already in 1977.
Erythropoietin has been in frequent clinical use for many years in patients with renal anaemia, in the case of nephrodialysis, in order to obtain fairly large quantities of autologous blood before planned operations, and it also appeared in press headlines as a doping agent.
Erythropoietin thereby proved to be exceptionally well tolerated. There should be mentioned as a relevant side-effect, in particular the often therapeutically desired stimulation of haematopoiesis with polyglobuly as well as arterial hypertension which is rarely to be observed. Both effects can be expected mainly after chronic erythropoietin administration. If required, these can be remedied relatively easily by medicinal treatment or blood-letting. Intolerance reactions or anaphylactic reactions are rarities with erythropoietin. WO 00/61164 discloses the use of EPO for the protection of neuronal tissue, in particular also of the central nervous system. It is mentioned in passing in this document that multiple sclerosis might also be treated with EPO.
There is considered by EPO or erythropoietin in the sense of the present invention and also in WO 00/61164, any erythropoietin, whether native or recombinant, from humans or another mammal, whether in native sequence or even after sequence changes or sequence shortening, any type of erythropoietin analogue, erythropoietin fragments or even substances binding to the erythropoietin receptor or erythropoietin agonists. The definition for erythropoietin or EPO according to WO 00/61164 is adopted in its entirety in the present application. Accordingly, by EPO and by erythropoietin any substance is meant, which can activate EPO-activated receptors in systemic application, i.e. also any type of variants, fragments or analogues. Further useable EPO variants are published for example in the following publications:
Leist et al., Science 2004, Vol. 305, pp. 239-242, WO 86/03520, WO 85/02610, WO 90/11354, WO 91/06667, WO 91/09955, WO 93/09222, WO 94/12650, WO 95/31560, WO 95/05465.
An overview of known EPO variants and analogues which can also be used in their entirety in the present invention and also of their known fields of use appears in Brines and Cerami, Nature Reviews, Neuroscience, June 2005, Vol. 6, pages 484-494.
It is not of particular relevance in the present invention whether the EPO analogues or erythropoietin fragments which are used have a haematopoietic effect or not. This is explained more precisely further on.
WO 00/61164 in fact discloses the use of EPO for the treatment of multiple sclerosis but indicates no experimental data or treatment regime.